Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain.
Assessment of sex specific endocrine disrupting effects in the prenatal and pre-pubertal rodent brain.
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DOI：
10.1016/j.jsbmb.2015.08.021
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Patisaul HB
中科院分区：
文献类型：
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作者：
Rebuli ME;Patisaul HB
大脑的性别差异几乎存在于大脑的每一个区域，是性二态行为以及大脑和行为障碍的基础。这些差异是在妊娠期和青春期早期组织起来的，在青春期之前就可以发现。内分泌干扰化合物(EDCs)干扰荷尔蒙的作用，因此产前暴露被假定为扰乱性别差异的形成，并导致存在性别偏见的儿科神经精神疾病的发病率增加。本文综述了内分泌细胞影响啮齿类动物大脑性别差异出现的能力的现有证据，重点是在青春期或青春期之前检测到的影响。使用PubMed检索同行评议的文献，并纳入2015年1月31日之前发表的所有相关论文。感兴趣的终点包括分子、细胞和神经解剖学效应。关于行为终点的研究没有包括在内，因为可以获得对该文献的大量综述。研究发现，雌激素类内皮细胞以性别、时间和暴露依赖的方式影响下丘脑。海马体似乎也容易受到双酚A和多氯联苯的内分泌干扰，尽管青春期前的文献中几乎没有证据可以得出任何关于性别特定影响的结论。孕期EDC暴露可改变胎儿神经发生和整个大脑，包括皮质和小脑的基因表达。现有的文献主要集中在少数几个特征良好的内分泌干扰物上，但关于新出现的污染物的数据很少。发育中的EDC暴露文献表明，早在胎儿时期就有神经发育改变的证据，甚至在青春期之前就观察到了整个大脑的性别特异性影响。
Brain sex differences are found in nearly every region of the brain and fundamental to sexually dimorphic behaviors as well as disorders of the brain and behavior. These differences are organized during gestation and early adolescence and detectable prior to puberty. Endocrine disrupting compounds (EDCs) interfere with hormone action and are thus prenatal exposure is hypothesized to disrupt the formation of sex differences, and contribute to the increased prevalence of pediatric neuropsychiatric disorders that present with a sex bias. Available evidence for the ability of EDCs to impact the emergence of brain sex differences in the rodent brain was reviewed here, with a focus on effects detected at or before puberty. The peer-reviewed literature was searched using PubMed, and all relevant papers published by January 31, 2015 were incorporated. Endpoints of interest included molecular cellular and neuroanatomical effects. Studies on behavioral endpoints were not included because numerous reviews of that literature are available. The hypothalamus was found to be particularly affected by estrogenic EDCs in a sex, time, and exposure dependent manner. The hippocampus also appears vulnerable to endocrine disruption by BPA and PCBs although there is little evidence from the pre-pubertal literature to make any conclusions about sex-specific effects. Gestational EDC exposure can alter fetal neurogenesis and gene expression throughout the brain including the cortex and cerebellum. The available literature primarily focuses on a few, well characterized EDCs, but little data is available for emerging contaminants. The developmental EDC exposure literature demonstrates evidence of altered neurodevelopment as early as fetal life, with sex specific effects observed throughout the brain even before puberty.